Skip to main content
SpringerLink
Log in

The essential fatty acid myristate causes severe growth retardation in Hpelo disruptants of the yeast Hansenula polymorpha

  • Original Paper
  • Published:
Archives of Microbiology Aims and scope Submit manuscript

Abstract

Myristate (C14:0) is an essential multi-functional fatty acid in a variety of organisms. We found that C14:0, but not other fatty acids, causes severe growth retardation in Hpelo1Δ and Hpelo2Δ mutants of the yeast Hansenula polymorpha, defective in elongation of very long-chain fatty acids. While transcription of HpELO1 and HpELO2 is transiently increased by C14:0, this was not found to be responsible for the growth retardation. Transcription of HpFAS1 and HpFAS2 encoding fatty acid synthase is repressed by C14:0, but this repression was also not found to be responsible for growth retardation. A screen for suppressors that resulted in restored growth of the Hpelo1Δ disruptant on media containing C14:0 identified two types of suppressors. One exhibited a defect in C14:0 uptake while the other did not. Molecular genetic and genomic analysis of these suppressor mutations is anticipated to shed new light on the processes of fatty acid transport and the crucial role of C14:0 in the growth of eukaryotic organisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Awaya J, Ohno T, Ohno H, Omura S (1975) Substitution of cellular fatty aicds in yeast cells by the antibiotic cerulenin and exogenous fatty acids. Biochim Biophys Acta 409:267–273

    PubMed  CAS  Google Scholar 

  • Bossie MA, Martin CE (1989) Nutritional regulation of yeast delta-9 fatty acid desaturase activity. J Bacteriol 171:6409–6413

    PubMed  CAS  Google Scholar 

  • Chirala SS (1992) Coordinated regulation and inositol-mediated and fatty acid mediated repression of fatty acid synthase genes in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 89:10232–10236

    Article  PubMed  CAS  Google Scholar 

  • Choi J-F, Martin CE (1999) The Saccharomyces cerevisiae FAT1 gene encodes an acyl-CoA synthethase that is required for maintenance of very long-chain fatty acid levels. J Biol Chem 274:4671–4683

    Article  PubMed  CAS  Google Scholar 

  • Cross GAM (1987) Eukaryotic protein modification and membrane attachment via phosphatidylinositol. Cell 48:179–181

    Article  PubMed  CAS  Google Scholar 

  • Cross FR, Garber EA, Pellman D, Hanafusa H (1984) A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and for cell transformation. Mol Cell Biol 4:1834–1842

    PubMed  CAS  Google Scholar 

  • Duronio RJ, Rudnick DA, Johnson RL, Linder ME, Gordon JI (1991) Myristic acid auxotrophy caused by mutation of Saccharomyces cerevisiae myristoyl-CoA: protein N-myristoyltransferase. J Cell Biol 266:10498–10504

    CAS  Google Scholar 

  • Durrens P, Revardel E, Bonneu M, Aigle M (1995) Evidence for branched pathway in the polarized cell division of Saccharomyces cerevisiae. Curr Genet 27:213–216

    Article  PubMed  CAS  Google Scholar 

  • Faergeman NJ, DiRusso CC, Elberger A, Knudsen J, Black PN (1997) Disruption of the Saccharomyces cerevisiae homologue to the murine fatty acid transport protein impairs uptake and growth on long-chain fatty acids. J Biol Chem 272:8531–8538

    Article  PubMed  CAS  Google Scholar 

  • Funabashi H, Kawaguchi A, Tomoda H, Omura S, Okuda S, Iwasaki S (1989) Binding site of cerulenin in fatty acid synthethase. J Biol Chem 105:751–755

    CAS  Google Scholar 

  • Gaigg B, Toulmay A, Schneither R (2006) Very long-chain fatty acid-containing lipids rather that sphingolipids per se are required for raft association and stable surface transport of newly synthesized plasma membrane ATPase in yeast. J Biol Chem 281:34135–34145

    Article  PubMed  CAS  Google Scholar 

  • Johnson DR, Knoll LJ, Levin DE, Gordon JI (1994) Saccharomyces cerevisiae contains four fatty acid activation (FAA) genes: and assessment of their in regulating protein N-myristoylation and cellular lipid metabolism. J Cell Biol 127:751–762

    Article  PubMed  CAS  Google Scholar 

  • Kaneko Y, Rueksomtawin K, Maekawa T, Harashima S (2003) Structural and functional analysis of the FAS1 gene encoding fatty acid synthase β-subunit in methylotrophic yeast Hansenula polymorpha. In: Murata N, Yamada M, Nishida I, Okuyama H, Sekiya J, Wada H (eds) Advanced research on plant lipids, Kluwer, London, pp 61–64

    Google Scholar 

  • Orme T, McIntyre J, Lynen F, Kuhn L, Schweizer E (1972) Fatty acid elongation in a mutant of Saccharomyces cerevisiae deficient in fatty acid synthethase. Eur J Biochem 24:407–415

    Article  PubMed  CAS  Google Scholar 

  • Oshiro T, Aiba H, Mizuno T (2003) A defect in a fatty acyl-CoA synthase gene, lcf1+, results in a decrease in viability after entry into the stationary phase in fission yeast. Mol Gen Genomics 269:437–442

    Article  CAS  Google Scholar 

  • Prasitchoke P, Kaneko Y, Bamba T, Fukusaki E, Kobayashi A, Harashima S (2007a) Identification and characterization of a very- long-chain fatty acid elongase gene in the methylotrophic yeast, Hansenula polymorpha. Gene 391:15–26

    Article  Google Scholar 

  • Prasitchoke P, Kaneko Y, Sugiyama M, Bamba T, Fukusaki E, Kobayashi A, Harashima S (2007b) Functional analysis of very long-chain fatty acid elongase gene, HpELO2, in the methylotrophic yeast Hansenula polymorpha. Appl Microbiol Biotechnol 76:417–427

    Article  PubMed  CAS  Google Scholar 

  • Simon SM, Aderem A (1992) Myristoylation of proteins in the yeast secretory pathway. J Biol Chem 267:3922–3931

    PubMed  CAS  Google Scholar 

  • Tong F, Black PN, Bivins L, Quackenbush S, Ctrnacta V, DiRusso CC (2006) Direct interaction of Saccharomyces cerevisiae Faa1p with the Omi/HtrA protease orthologue Ynm3p alters lipid homeostasis. Mol Gen Genomics 275:330–343

    Article  CAS  Google Scholar 

  • Towler DA, Adams SP, Eubanks SR, Towery DS, Jackson Machelski E, Glaser L, Gordon JI (1987) Purification and characterization of yeast myristoyl CoA:protein N-myristolyltransferase. Proc Natl Acad USA 84:2708–2712

    Article  CAS  Google Scholar 

  • Watkins PA, Lu J-F, Steinberg SJ, Gould SJ, Smith KD, Braiterman LT (1998) Disuprtion of the Saccharomyces cerevisiae FAT1 gene decreases very long-chain fatty acyl-CoA synthethase and elvates intracellular very long-chain fatty acid concentrations. J Biol Chem 273:18210–18219

    Article  PubMed  CAS  Google Scholar 

  • Zou Z, DiRusso CC, Ctrnacta V, Black PN (2002) Fatty acid transport in Saccharomyces cerevisiae: Directed mutagenesis of FAT1 distinguishes the biochemical activities associated with Fat1p. J Biol Chem 277:31062–31071

    Article  PubMed  CAS  Google Scholar 

  • Zou Z, Tong F, Faergeman NJ, Børsting C, Black PN, DiRusso CC (2003) Vectorial acylation in Saccharomyces cerevisiae: Fat1p and fatty acyl-CoA synthetase and interacting components of a fatty acid import complex. J Biol Chem 278:16414–16422

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Masayuki Komori and Dr. Minetaka Sugiyama for fruitful discussions.

Author information

Authors and Affiliations

  1. Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Phatthanon Prasitchoke, Yoshinobu Kaneko, Ei-ichiro Fukusaki, Akio Kobayashi & Satoshi Harashima

  2. Department of Applied Environmental Biology, Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, 565-0871, Japan

    Takeshi Bamba

Authors
  1. Phatthanon Prasitchoke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshinobu Kaneko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takeshi Bamba
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ei-ichiro Fukusaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akio Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Satoshi Harashima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satoshi Harashima.

Additional information

Communicated by Geoffrey Turner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prasitchoke, P., Kaneko, Y., Bamba, T. et al. The essential fatty acid myristate causes severe growth retardation in Hpelo disruptants of the yeast Hansenula polymorpha . Arch Microbiol 189, 297–304 (2008). https://doi.org/10.1007/s00203-007-0317-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00203-007-0317-7

Keywords

Search

Navigation